Pejler, Gunnar
- Department of Animal Biosciences, Swedish University of Agricultural Sciences
Research article2013Peer reviewed
Hendrix, Sven; Kramer, Peter; Pehl, Debora; Warnke, Katharina; Boato, Francesco; Nelissen, Sofie; Lemmens, Evi; Pejler, Gunnar; Metz, Martin; Siebenhaar, Frank; Maurer, Marcus
Mast cells (MCs) are found abundantly in the brain and the meninges and play a complex role in neuroinflammatory diseases, such as stroke and multiple sclerosis. Here, we show that MC-deficient Kit(W)/Kit(W-v) mice display increased neurodegeneration in the lesion area after brain trauma. Furthermore, MC-deficient mice display significantly more brain inflammation, namely an increased presence of macrophages/microglia, as well as dramatically increased T-cell infiltration at days 4 and 14 after injury, combined with increased astrogliosis at day 14 following injury. The number of proliferating Ki67(+) macrophages/microglia and astrocytes around the lesion area is more than doubled in these MC-deficient mice. In parallel, MC-deficient Kit(W-sh/W-sh) mice display increased presence of macrophages/microglia at day 4, and persistent astrogliosis at day 4 and 14 after brain trauma. Further analysis of mice deficient in one of the most relevant MC proteases, i.e., mouse mast cell protease 4 (mMCP-4), revealed that astrogliosis and T-cell infiltration are significantly increased in mMCP-4-knockout mice. Finally, treatment with an inhibitor of mMCP-4 significantly increased macrophage/microglia numbers and astrogliosis. These data suggest that MCs exert protective functions after trauma, at least in part via mMCP-4, by suppressing exacerbated inflammation via their proteases.-Hendrix, S., Kramer, P., Pehl, D., Warnke, K., Boato, F., Nelissen, S., Lemmens, E., Pejler, G., Metz, M., Siebenhaar, F., Maurer, M. Mast cells protect from post-traumatic brain inflammation by the mast cell-specific chymase mouse mast cell protease-4. FASEB J. 27, 920-929 (2013). www.fasebj.org
entorhinal cortex lesion; mMCP-4; protease; T cells
FASEB Journal
2013, Volume: 27, number: 3, pages: 920-929 Publisher: FEDERATION AMER SOC EXP BIOL
Neurosciences
DOI: https://doi.org/10.1096/fj.12-204800
https://res.slu.se/id/publ/52768